The training and research components of this application for a Scientist Development Award for New Minority Faculty are designed to prepare the applicant for a career as an independent investigator at the interface of the basic and clinical sciences. The career development plan, modeled after the Ph.D. program in biological sciences, will provide the scientific knowledge base and specific laboratory techniques required to conduct the proposed research. Supervised case management in addition to tutorials in hematology, cardiology, and psychiatric assessment will develop the applicant's clinical skills. The research plan focuses on the relationship between major mood disorders and thrombotic disease. Not only are platelets a source of vasoactive mediators that regulate vascular tone, but they also play a role in intravascular thrombus formation and dynamic coronary constriction that results in myocardial ischemia. There is considerable evidence that patients with ischemic heart disease (IHD) and concurrent major depression have a less favorable prognosis than patients with IHD alone. Recent studies have revealed that major depression is a very significant risk factor for death after myocardial infarction and stroke and not simply a nonspecific emotional response to cardiovascular illness. The overall objective of the proposed work is to investigate further this interaction between major depression and the hemostatic system, especially major depression. The research aims are to determine: 1) whether depressed patients without cardiovascular disease exhibit exaggerated platelet reactivity under basal conditions, 2) whether platelet responsiveness to orthostatic challenge and standard inducers of aggregation are altered in patients with major depression, and 3) if pharmacologic treatment of depressed patients with paroxetine (a potent and selective serotonin reuptake inhibitor) is associated with alteration of platelet responsiveness to orthostatic challenge, and to standard inducers of aggregation. To accomplish these aims, platelet function and severity of depression willbe evaluated longitudinally before and after treatment with either placebo or paroxetine. Additionally, the in vitro activity of paroxetine on platelet activity will be evaluated. Future investigators would expand these findings to depression by evaluation and treatment of depressed patients at risk for IHD (e.g., those with hypertension, hyperlipidemia, etc...) and patient post-myocardial infarction with comorbid depression. These studies will provide novel information on the biological basis for the apparent increased vulnerability of depressed patients to IHD.